Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

When diluting bulk extracts, use of Sterile Diluent for Allergenic Extracts or Sterile Diluent for Allergenic Extracts Normal Saline with HSA (albumin saline) is recommended. Dilutions should be made with sterile disposable syringes using aseptic technique. Commonly, 10 fold dilutions are used to achieve a desired concentration for initiation and continuation of immunotherapy. For example, transferring 0.5 mL of a 10,000 PNU/mL extract into 4.5 mL of diluent will yield 5 mL of extract at 1,000 PNU/mL. For weight volume products, a 1:100 w/v dilution may be prepared from a 1:10 w/v by transferring 0.5 mL of the 1:10 w/v to 4.5 mL of diluent. Prepare as many additional serial dilutions as necessary to reach the appropriate concentration.

Starting dose for immunotherapy is related directly to a patient's sensitivity as determined by carefully executed skin testing. Degree of sensitivity can be established by determination of D5011. A general rule is to begin at 1/10 of the dose that produces sum of erythema of 50 mm (approximately a 2+ positive skin test reaction).

For example, if a patient exhibits a 2+ intradermal reaction to 1 AU/mL, the first dose should be no higher than 0.05 mL of 0.1 AU/mL. Dosage may be increased by 0.05 mL each time until 0.5 mL is reached, at which time the next 10-fold more concentrated dilution can be used, beginning with 0.05 mL, if no untoward reaction is observed.

Interval between doses in the early stages of immunotherapy is no more than once to twice a week, and may gradually be increased to once every two weeks. Generally, maintenance injections may be given as infrequently as once every two weeks to once a month.

Injections are given subcutaneously, preferably in the arm. It is advantageous to give injections in alternate arms and routinely in the same area. In some patients, a local tolerance to the allergen may develop thus preventing a possible severe local reaction.

Formal stability studies for diluted and undiluted forms of unstandardized extracts have not been performed; therefore, it is recommended that minimal amounts of the concentrate be diluted so that the diluted product is used up within a relatively short period of time; i.e., preferably not more than four weeks.

PRE-SEASONAL METHOD OF TREATMENT

Treatment of hay fever by the pre-seasonal method should be started 6-10 weeks prior to the usual onset of symptoms. Therapy should be started early enough to permit a graduated series of doses at 2-7 day intervals. It is recommended that the larger doses be spaced 5-7 days apart.

Some physicians continue therapy into or through the season by repeating a reduced or MAINTENANCE dose at weekly or biweekly intervals. If during the season, hay fever symptoms develop, relief may be provided by giving supplemental treatment. If the last dose was well-tolerated and not more than 2 weeks has elapsed since it was given, this dose may be given again and repeated every 4 to 7 days.

PERENNIAL TREATMENT

The patient's tolerance to the offending pollen or pollens is first established by the injection of a series of graduated doses as outlined in the PRE-SEASONAL METHOD, not necessarily given pre-seasonally, since perennial therapy may be begun at any time. After completion of the ascending series of injections, from ¼ to ½ of the highest well-tolerated dose is continued at 2 to 3 week intervals throughout the year. Shortly before the usual onset of symptoms (4 to 5 weeks prior to the season), the interval between injections is shortened and the dosage is gradually increased, according to the Pre-Seasonal schedule, until maximum well-tolerated dose is again attained. This top dose should be reached just before the usual onset of symptoms at which time the treatment is discontinued. If patient's symptoms persist, therapy may be continued at a reduced dosage level, usually ¼ to ½ of the top dose.

DOSAGE ADJUSTMENTS

For Products Containing Short Ragweed.

In transferring patients from unstandardized to standardized product, the physician should establish the potency relationships, perhaps by comparative skin testing, prior to injecting the first standardized dose.

AgE is important in adjusting dosage of Short Ragweed extracts to accurately transfer a patient from older extracts to fresher material. In such cases, the dosage of AgE should be considered in addition to the W/V dilution or protein nitrogen units. Antigen E concentration continuously declines in Short Ragweed Pollen extracts at a rate that varies with the formulation of the product. Aqueous extracts retain Antigen E potency less effectively than glycerin 50% (v/v) extracts. These differences are reflected in the expiration date declared on the vial. The continuous decline should be considered. Also, where ragweed is a component of an allergen mixture, clinical response to the other components must be considered in adjustment of dosage based on AgE content alone. The usual course of immunotherapy is three to five years.

Caution: A small percent of individuals allergic to Short Ragweed are more sensitive to minor antigens such as Ra3 Ra5 than AgE. There is no correlation between the amount of these antigens and either AgE or PNU content.

NOTE: For extracts of Short Ragweed or equal part mixture of Short and Tall Ragweed refer to AgE dosage schedule. The AgE content for those products is indicated on the vial label. The physician may use the formula below to determine the AgE dosage for each injection.